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Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes
Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in n...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473044/ https://www.ncbi.nlm.nih.gov/pubmed/23091610 http://dx.doi.org/10.1371/journal.pone.0047137 |
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author | Ziebarth, Jesse D. Bhattacharya, Anindya Cui, Yan |
author_facet | Ziebarth, Jesse D. Bhattacharya, Anindya Cui, Yan |
author_sort | Ziebarth, Jesse D. |
collection | PubMed |
description | Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in non-coding regions. Here, we study somatic mutations in 3′UTRs of genes that have been identified in four cancers and computationally predict how they may alter miRNA targeting, potentially resulting in dysregulation of the expression of the genes harboring these mutations. We find that somatic mutations create or disrupt putative miRNA target sites in the 3′UTRs of many genes, including several genes, such as MITF, EPHA3, TAL1, SCG3, and GSDMA, which have been previously associated with cancer. We also integrate the somatic mutations with germline mutations and results of association studies. Specifically, we identify putative miRNA target sites in the 3′UTRs of BMPR1B, KLK3, and SPRY4 that are disrupted by both somatic and germline mutations and, also, are in linkage disequilibrium blocks with high scoring markers from cancer association studies. The somatic mutation in BMPR1B is located in a target site of miR-125b; germline mutations in this target site have previously been both shown to disrupt regulation of BMPR1B by miR-125b and linked with cancer. |
format | Online Article Text |
id | pubmed-3473044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34730442012-10-22 Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes Ziebarth, Jesse D. Bhattacharya, Anindya Cui, Yan PLoS One Research Article Determining the functional impact of somatic mutations is crucial to understanding tumorigenesis and metastasis. Recent sequences of several cancers have provided comprehensive lists of somatic mutations across entire genomes, enabling investigation of the functional impact of somatic mutations in non-coding regions. Here, we study somatic mutations in 3′UTRs of genes that have been identified in four cancers and computationally predict how they may alter miRNA targeting, potentially resulting in dysregulation of the expression of the genes harboring these mutations. We find that somatic mutations create or disrupt putative miRNA target sites in the 3′UTRs of many genes, including several genes, such as MITF, EPHA3, TAL1, SCG3, and GSDMA, which have been previously associated with cancer. We also integrate the somatic mutations with germline mutations and results of association studies. Specifically, we identify putative miRNA target sites in the 3′UTRs of BMPR1B, KLK3, and SPRY4 that are disrupted by both somatic and germline mutations and, also, are in linkage disequilibrium blocks with high scoring markers from cancer association studies. The somatic mutation in BMPR1B is located in a target site of miR-125b; germline mutations in this target site have previously been both shown to disrupt regulation of BMPR1B by miR-125b and linked with cancer. Public Library of Science 2012-10-16 /pmc/articles/PMC3473044/ /pubmed/23091610 http://dx.doi.org/10.1371/journal.pone.0047137 Text en © 2012 Ziebarth et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ziebarth, Jesse D. Bhattacharya, Anindya Cui, Yan Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title | Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title_full | Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title_fullStr | Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title_full_unstemmed | Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title_short | Integrative Analysis of Somatic Mutations Altering MicroRNA Targeting in Cancer Genomes |
title_sort | integrative analysis of somatic mutations altering microrna targeting in cancer genomes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473044/ https://www.ncbi.nlm.nih.gov/pubmed/23091610 http://dx.doi.org/10.1371/journal.pone.0047137 |
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